The objectives of this project are to determine the relative contributions of levo, alpha-acetylmethadol (LAAM) and its active metabolites to the pharmacological actions of the drug as can be deduced from dispositional and pharmacokinetic data obtained in rat, baboon and man. In rats pharmacokinetic studies will be carried out in conjunction with the measurement of "analgesia" (tail-flick response) and other pharmacological effects seen following acute and chronic dosing with LAAM. The baboon, prepared with a cholecystopexy, will provide a model to be used to evaluate the role of the enterohepatic system in the disposition and pharmacokinetics of LAAM. Clinical analgesic assays of parenteral and oral LAAM and of parenteral methadone will be carried out in conjucntion with pharmacokinetic studies in cancer patients with pain. Pharmacokinetic parameters at steady state will be determined from studies in LAAM maintenance patients. The analytical methods used in these studies will include: high-pressure liquid chromatography, radiotracer techniques, mass spectometry, gas-liquid chromatography and radioimmunoassay. These methods together with solvent extraction, thin-layer and column chromatography will provide quantitative and qualitative information on the disposition of LAAM in these three species.